title: Atopy history and the genomics of wheezing after influenza vaccination in children 6-59 months of age.
abstract: BACKGROUND
  A multinational clinical trial compared the safety and efficacy of intranasal trivalent live attenuated influenza vaccine (LAIV) with intramuscular trivalent inactivated vaccine (TIV) in very young children prior to the 2004-5 influenza season [1]. Wheezing was noted more often in recipients of LAIV and laboratory-confirmed influenza infection was noted more often in recipients of TIV. We sought to determine whether epidemiologic or genetic factors were associated with these outcomes.
  
  
  METHODS
  Atopy surveys and DNA collections were performed in trial participants at two United States sites, Nashville, TN and Boston, MA. DNA samples were genotyped on Illumina Infinium 610 or 660-Quad. Standard allelic tests of association were performed.
  
  
  RESULTS
  At the Nashville and Boston sites, a total of 99 children completed the trial, 6 (1 TIV, 5 LAIV) developed medically attended wheezing within 42 days following vaccination, and 8 (5 TIV, 3 LAIV) developed laboratory-confirmed influenza during the season. Eighty-one surveys and 70 DNA samples were collected. Family history of asthma (p=0.001) was associated with wheezing after vaccination. Of 468,458 single nucleotide polymorphisms tested in the genome-wide association study (GWAS), none achieved genome-wide significance for either wheezing after vaccination or laboratory-confirmed influenza infection.
  
  
  CONCLUSIONS
  Family history of asthma appears to be a risk factor for wheezing after influenza vaccination. Given the limitations of the sample size, our pilot study demonstrated the feasibility of performing a GWAS but was not able to determine genetic polymorphisms associated with wheezing after influenza immunization.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, CCC-5323 Medical Center North, Nashville, TN 37232, USA.
authors.forename: E Kathryn
authors.initials: EK
authors.lastname: Miller
authors.forename: Logan
authors.initials: L
authors.lastname: Dumitrescu
authors.forename: Chelsea
authors.initials: C
authors.lastname: Cupp
authors.forename: Stacy
authors.initials: S
authors.lastname: Dorris
authors.forename: Sallee
authors.initials: S
authors.lastname: Taylor
authors.forename: Robert
authors.initials: R
authors.lastname: Sparks
authors.forename: Diane
authors.initials: D
authors.lastname: Fawkes
authors.forename: Virginia
authors.initials: V
authors.lastname: Frontiero
authors.forename: Anne M
authors.initials: AM
authors.lastname: Rezendes
authors.forename: Colin
authors.initials: C
authors.lastname: Marchant
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Edwards
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
mesh_terms: D001249:Asthma / Q000150:complications; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002986:Clinical Trials as Topic; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007223:Infant; D007252:Influenza Vaccines / Q000009:adverse effects* / Q000276:immunology; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control; D008297:Male; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D012135:Respiratory Sounds / Q000235:genetics*; D012307:Risk Factors
chemical_list: D007252:Influenza Vaccines